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Thermodynamic analysis of metabolic networks has recently generated increasing interest for its ability to add constraints on metabolic network operation, and to combine metabolic fluxes and metabolite measurements in a mechanistic manner. Concepts for the calculation of the change in Gibbs energy of biochemical reactions have long been established. However, a concept for incorporation of cross-membrane transport in these calculations is still missing, although the theory for calculating thermodynamic properties of transport processes is long known. Here, we have developed two equivalent equations to calculate the change in Gibbs energy of combined transport and reaction processes based on two different ways of treating biochemical thermodynamics. We illustrate the need for these equations by showing that in some cases there is a significant difference between the proposed correct calculation and using an approximative method. With the developed equations, thermodynamic analysis of metabolic networks spanning over multiple physical compartments can now be correctly described.

Recent advances in cancer research have identified critical angiogenic signaling pathways and the influence of the extracellular matrix on endothelial cell migration. These findings provide us with insight into the process of angiogenesis that can facilitate the development of effective computational models of sprouting angiogenesis. In this work, we present the first three-dimensional model of sprouting angiogenesis that considers explicitly the effect of the extracellular matrix and of the soluble as well as matrix-bound growth factors on capillary growth. The computational model relies on a hybrid particle-mesh representation of the blood vessels and it introduces an implicit representation of the vasculature that can accommodate detailed descriptions of nutrient transport. Extensive parametric studies reveal the role of the extracellular matrix structure and the distribution of the different vascular endothelial growth factors isoforms on the dynamics and the morphology of the generated vascular networks.

Many nucleic acid stains show a strong fluorescence enhancement upon binding to double-stranded DNA. Here we exploit this property to perform superresolution microscopy based on the localization of individual binding events. The dynamic labeling scheme and the optimization of fluorophore brightness yielded a resolution of ∼14 nm (fwhm) and a spatial sampling of 1/nm. We illustrate our approach with two different DNA-binding dyes and apply it to visualize the organization of the bacterial chromosome in fixed Escherichia coli cells. In general, the principle of binding-activated localization microscopy (BALM) can be extended to other dyes and targets such as protein structures.